A case of pyogenic meningitis caused by Bacteroidesfragilis in a 72-year-old woman is reported. Although the isolate was susceptible to thiamphenicol, the ...
JOURNAL OF CLINICAL MICROBIOLOGY, Sept. 1986, p. 472-473 0095-1137/86/090472-02$02.00/0 Copyright © 1986, American Society for Microbiology
Vol. 24, No. 3
Bacteroides fragilis Meningitis Successfully Treated with Metronidazole after a Previous Failure with Thiamphenicol FRANCISCO SORIANO,l* JOSE M. AGUADO,2 JESUS TORNERO,3 MANUEL L. FERNANDEZ-GUERRERO,2 AND JOSE L. GOMEZ-GARCtS' Departments of Microbiology,' Internal Medicine,2 and Rheumatology,3 Fundacion Jimenez Diaz, 28040 Madrid, Spain Received 13 February 1986/Accepted 27 May 1986
A case of pyogenic meningitis caused by Bacteroidesfragilis in a 72-year-old woman is reported. Although the isolate was susceptible to thiamphenicol, the patient did not respond to this drug. Metronidazole, which showed high bactericidal activity, was administered and achieved sterilization of the cerebrospinal fluid and complete clinical response.
Meningitis caused by obligate anaerobes is an infrequently reported disease, and no more than 100 reports have been published (4, 6). Bacteroides spp. are hardly ever involved in this clinical situation, and, to our knowledge, fewer than 10 cases of meningitis by Bacteroides fragilis have been reported (1, 2, 4, 6, 8; P. M. Hawkey and L. A. Jewes, Letter, J. Clin. Microbiol, 22:325, 1985). Most cases occurred in children in association with a focus of suppuration in the middle ear or the sinuses of the skull (1, 6, 8), and cases are very rare in the elderly (2, 6; Hawkey and Jewes, Letter, J. Clin. Microbiol. 22:325, 1985). An illustrative case of B. fragilis meningitis, probably related to infection of a decubitus ulcer, in an elderly patient is reported. A 72-year-old woman came to our hospital with a 7-day history of fever and stupor. She had been diagnosed as having rheumathoid arthritis 15 years before and recently had been bedridden, so that a decubitus ulcer had appeared in the sacrus region. The patient had been receiving 20 mg of methylprednisolone per day for 5 years. Upon admission, she was confused and febrile with a temperature of 38.6°C and had a purulent and fetid discharge from the decubitus ulcer which was immediately treated topically without any bacteriological study. There was neither nuchal rigidity nor other neurological signs. No abnormalities were found on physical examination except those related to the patient's underlying disease. There was no evidence of any infectious foci except the decubitus ulcer. Four blood cultures were obtained on admission, but no antimicrobial treatment was started. A cerebral computerized axial tomography scan with intravenous contrast showed no abnormalities. Her clinical condition remained unchanged 3 days after admission. Cerebrospinal fluid (CSF) was obtained and found to be slightly turbid, with a leukocyte count of 300/,l with predominant segmented neutrophils (95%), protein and glucose contents of 95 and 6 mg/dl, respectively (serum glucose content, 190 mgldl). A Gram-stained smear revealed many pale, irregularly stained, gram-negative, and pleomorphic bacilli, which suggested the possibility of anaerobic bacilli. Thus, the CSF was centrifuged, and the sediment was inoculated onto chocolate agar and blood agar plates which were incubated at 35°C both aerobically and anaerobically. After 24 h of incubation, only the plates incubated anaerobically yielded luxuriant growth of obligate anaerobic and *
gram-negative bacilli. The isolate was nonhemolytic, nonpigmented, nonmotile, and catalase positive. Growth in 20% bile was positive, esculin hydrolysis was positive, and an indole test was negative. The organism fermented glucose, maltose, and sucrose. It did not ferment arabinose, rhamnose, salicin, or trehalose. The diagnostic antibiotic disk method showed that the organism was susceptible to erythromycin (60 ,ug) and rifampin (15 ,ug) but resistant to colistin sulfate (10 ,ug), penicillin G (2 U), kanamycin (1,000 ,ug), and vancomycin (5 rag). The biochemical and antimicrobial susceptibility patterns were consistent with those for B. fragilis (3). The four blood cultures taken on admission were positive for the same microorganisms, but aerobic and anaerobic cultures of the decubitus ulcer taken 5 days after admission failed to grow any bacteria. The MICs and MBCs of thiamphenicol and metronidazole were determined by the macrobroth dilution method (10); B. fragilis ATCC 25285 was used as the control. The susceptibility test results are shown in Table 1. Empiric therapy was begun on day 3 with thiamphenicol (1.5 g/6 h intravenously). After 1 week of therapy with this drug (days 3 to 10), the clinical condition of the patient was unchanged, and CSF cultures remained positive, although the concentration of thiamphenicol in the CSF as measured by high-performance liquid chromatography was above the MIC for the bacterium. Parenteral metronidazole was begun on day 10 at a dosage of 0.5 g/6 h, and clinical improvement, absence of fever, and sterilization of the CSF were obtained 4 days later. Treatment with this drug was maintained for 20 days, resulting in discharge of the patient on day 35 in a satisfactory condition and with sterilization of her CSF, although polymorphonuclear leukocytosis persisted on days 43 and 58. Four months after admission, the patient was doing very well, and although minimal abnormalities were TABLE 1. Antimicrobial susceptibility of the B. fragilis strain isolated from the CSF of the patient MIC (,uLg/ml) MBC (ptg/ml)
Corresponding author. 472
Organism
Thiamphenicol
Metronidazole
Thiamphenicol
Metronidazole
B. fragilis patient isolate B. fragilis ATCC 25285
4
0.25
>128
0.5
4
0.5
>128
1
VOL. 24, 1986
NOTES
473
TABLE 2. Evolutive laboratory data and antimicrobial therapy of patient with B. fragilis meningitis CSF No. of days after admission
Aniirbatramn Antimicrobialtreatment
0 3 7 10
14 43 58 120
Blo
culture
gMl Drug level(p.gIml)'
No. of leukocytes per,l (% polymorphonuclear leukocytes)
Glucose
(mgdl)
(mgdl)
300 (95) 150 (90) 2,000 (90)
6 53 7
95 90 70
+ + +
12.7 11.3
67 (70) 58 (80) 266 (70) 8
26 66 56 35
100 100 70 20
-
6.2
Protein
Culture
Thiamphenicol
Metronidazole
+
Thiamphenicol (1.5) Thiamphenicol (1.5) Thiamphenicol (1.5) Metronidazole (0.5) Metronidazole (0.5)
-
23.8
-
-
Determined by high-performance liquid chromatography.
still present in the CSF, neurological examination revealed no focal or meningeal signs and a new cerebral computerized axial tomography scan showed no abnormalities. The main evolutive laboratory data and antibiotic therapy of the patient are shown in Table 2. The suspected pathogenic sequence in our patient was normal intestinal colonization of the decubitus ulcer with B. fragilis, although this was not proven due to the rapid and effective local treatment of the lesion; however, this microorganism has been shown in practically all the decubitus ulcers bacteriologically studied (5). Bacteremia by this microorganism was documented on admission and probably occurred as a result of the decubitus ulcer seeding the central nervous system. Thiamphenicol, an analog of chloramphenicol, is also recommended for patients with anaerobic infections (9). The levels in the CSF of this drug obtained after the abovementioned dosage were three times higher than the MIC against the bacterium but very much lower than the MBC. On the other hand, metronidazole levels in the CSF, as determined by high-performance liquid chromatography, were about 100 times higher than the MIC and 50 times higher than the MBC against the B. fragilis isolate. The failure of chloramphenicol to control B. fragilis meningitis has already been reported (1, 8), and we believe that the results obtained in our case with thiamphenicol add significant clinical evidence to experimental studies that have shown that bactericidal activity is required to cure some meningitis (11). The convenience of inoculating anaerobic media in bacteriological studies of meningitis has been debated, because some cases are culture negative in the absence of previous antimicrobial treatment and anaerobic meningitis could be overlooked if the CSF is not adequately processed. However, researchers who perform anaerobic cultures routinely consider such meningitis an exceptional clinical condition (2; Hawkey and Jewes, Letter, J. Clin. Microbiol. 22:235, 1985) and recommend anaerobic study of the CSF only in patients with identifiable risk factors (6; Hawkey and Jewes, Letter, J. Clin. Microbiol. 22:325, 1985). A decubitus ulcer should be considered a risk factor to be added to the previously suggested factors for anaerobic meningitis (6). As such patients may not be easily identifiable by the laboratory, all specimnens should be cultured anaerobically, as is recommended by some researchers (4, 7), or at least into thiogly-
colate broth medium, although an experienced microbiologist may in some cases suspect anaerobic infection after careful evaluation of a Gram stain of the CSF. We are grateful to Isabel Garcia Luque, Departamento de Microbiologia de la Facultad de Medicina de Sevilla, Seville, Spain,
who determined the levels of the antimicrobials agents in the CSF by
high-performance liquid chromatography. LITERATURE CITED 1. Berman, B. W., F. H. King, Jr., D. S. Rubensteih, and S. S. Long. 1978. Bacteroidesfragilis meningitis in a neonate successfully treated with metronidazole. J. Pediatr. 93:793-795. 2. Chattopadhyay, B. 1977. Bacteroidesfragilis meningitis. Lancet i:1371. 3. Finegold, S. M., and M. A. C. Edelstein. 1985. Gram-negative, nonsporeforming anaerobic bacilli, p. 450-460. In E; H. Lennette, A. Balows, W. J. Hausler, Jr., and H. J. Shadomy (ed.), Manual of clinical microbiology, 4th ed. American Society for Microbiology, Washington, D.C. 4. Finegold, S. M., and W. J. Martin. 1982. Microorganisms encountered in cerebrospinal fluid, p. 116-127. In Diagnostic microbiology, 6th ed. The C. V. Mosby Co., St. Louis. 5. Gorbach, S. L. 1985. Bacteroides species, p. 1368-1373. In G. L. Mandell, R. G. Douglas, Jr., and J. E. Bennett (ed.), Principles and practice of infectious diseases, 2nd ed. John Wiley & Sons, Inc., New York. 6. Heerema, M. S., M. E. Ein, D. M. Musher, M. W. Bradshaw, and T. W. Williams, Jr. 1979. Anaerobic bacterial meningitis. Am. J. Med. 67:219-227. 7. Isenberg, H. D., J. A. Washington II, A. Balows, and A. C. Sonnenwirth. 1985. Collection, handling, and processing of specimens, p. 73-98. In E. H. Lennette, A. Balows, W. J. Hausler, Jr., and H. J. Shadomy (ed.), Manual of clinical microbiology, 4th ed. American Society for Microbiology, Washington, D.C. 8. Odugbemi, T., S. A. Jatto, and K. Afolabi. 1985. Bacteroides fragilis meningitis. J. Clin. Microbiol. 21:282-283. 9. Reiner, R. 1982. Chemotherapeutic properties of antibiotics, p. 67-91. In Antibiotics. An introduction. Editions Roche, Basel. 10. Sutter, V. L. 1985. Susceptibility testing of anaerobes, p. 988-990. In E. H. Lennette, A. Balows, W. J. Hausler, Jr., and H. J. Shadomy (ed.), Manual of clinical niicrobiology, 4th ed. American Society for Microbiology, Washington, D.C. 11. Tauber, M. G., C. A. Doroshow, C. J. Hackbarth, M. G. Rusnak, T. A. Drake, and M. A. Sande. 1984. Antibacterial activity of beta-lactam antibiotics in experimental meningitis due to Streptococcus pneumoniae. J. Infect. Dis. 149:568-574.
